Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients

David Michalovich, Noelia Rodriguez-Perez, Sylwia Smolinska, Michal Pirozynski, David Mayhew, Sorif Uddin, Stephanie Horn, Milena Sokolowska, Can Altunbulakli, Andrzej Eljaszewicz, Benoit Pugin, Weronika Barcik, Magdalena Kurnik-Lucka, Ken A. Saunders, Karen D. Simpson, Peter Schmid-Grendelmeier, Ruth Ferstl, Remo Frei, Noriane Sievi, Malcolm Kohler, Pawel Gajdanowicz, Katrine B. Graversen, Katrine Lindholm Bøgh, Marek Jutel, James R. Brown, Cezmi A. Akdis, Edith M. Hessel and Liam O’Mahony ()
Additional contact information
David Michalovich: Adaptive Immunity Research Unit, GSK R&D
Noelia Rodriguez-Perez: University of Zurich
Sylwia Smolinska: Wroclaw Medical University
Michal Pirozynski: Centre of Postgraduate Medical Education
David Mayhew: Computational Biology, Human Genetics, GSK R&D
Sorif Uddin: Adaptive Immunity Research Unit, GSK R&D
Stephanie Horn: Target and Pathway Validation, Target Sciences, GSK R&D
Milena Sokolowska: University of Zurich
Can Altunbulakli: University of Zurich
Andrzej Eljaszewicz: University of Zurich
Benoit Pugin: University of Zurich
Weronika Barcik: University of Zurich
Magdalena Kurnik-Lucka: Jagiellonian University Medical College
Ken A. Saunders: Adaptive Immunity Research Unit, GSK R&D
Karen D. Simpson: Adaptive Immunity Research Unit, GSK R&D
Peter Schmid-Grendelmeier: Christine Kühne-Center for Allergy Research and Education (CK-CARE)
Ruth Ferstl: University of Zurich
Remo Frei: University of Zurich
Noriane Sievi: University Hospital of Zurich
Malcolm Kohler: University Hospital of Zurich
Pawel Gajdanowicz: Wroclaw Medical University
Katrine B. Graversen: Technical University of Denmark
Katrine Lindholm Bøgh: Technical University of Denmark
Marek Jutel: Wroclaw Medical University
James R. Brown: Computational Biology, Human Genetics, GSK R&D
Cezmi A. Akdis: University of Zurich
Edith M. Hessel: Adaptive Immunity Research Unit, GSK R&D
Liam O’Mahony: University of Zurich

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.

Date: 2019
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DOI: 10.1038/s41467-019-13751-9

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